Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

SCOPE: Women seeking alternatives to hormone‐replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8‐prenylnaringenin (8‐PN), a potent phytoestrogen, the related flavanones 6‐prenylnaringenin and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN). METHODS AND RESULTS: After chemically and biologically standardizing an extract of spent hops to these marker compounds, an escalating dose study was carried out in menopausal women to evaluate safety and pharmacokinetics. 8‐PN, 6‐prenylnaringenin, IX, and XN, sex hormones, and prothrombin time were determined in blood samples and/or 24 h urine samples. There was no effect on sex hormones or blood clotting. The maximum serum concentrations of the prenylated phenols were dose‐dependent and were reached from 2 to 7 h, indicating slow absorption. The marker compounds formed glucuronides that were found in serum and urine. Secondary peaks at 5 h in the serum concentration‐time curves indicated enterohepatic recirculation. The serum concentration‐time curves indicated demethylation of IX to form 8‐PN and cyclization of XN to IX. Slow absorption and enterohepatic recirculation contributed to half‐lives exceeding 20 h. CONCLUSION: This human study indicated long half‐lives of the estrogenic and proestrogenic prenylated phenols in hops but no acute toxicity.